The overall objective of the proposed research is to investigate the physiological and pathological significance of the interaction between intermediate products of fibrinogen-fibrin conversion and several cell types, especially platelets. The involvement of fibrin in a variety of biological processes such as inflammation, tissue repair, fibrinoid degeneration and metastases of tumors indicates that fibrin probably interacts with cells other than platelets. Our recent experiments confirmed this with fibroblasts and PMN granulocytes by demonstrating that these cells adhere to polymerizing fibrin and eventually cause retraction of fibrin. The project has the following long term objectives: (a) identification of components of polymerizing fibrin and of platelet membranes which do interact; identification of the specific inhibitors of platelet-fibrin interaction; explanation of the platelet-fibrin interaction at the molecular level including fibrin retraction and fibrin stabilization by platelets. (b) Comparison of platelets with other cells (fibroblasts, endothelial cells, PMN granulocytes, lymphocytes and cancer cells) with respect to the interaction with fibrin. (c) Identification of the effects of fibrin-cell interaction which may be of pathological or of physiological significance and the study of cell-fibrin interaction in pathological states involving platelets and other cells. (d) Effects of polymerizing fibrin on platelets and on other cells in vivo.